Rocket Pharmaceuticals (RCKT) Status Update summary

Preliminary phase I results and clinical insights

• RP-A601 at 8E13 vg/kg showed a favorable safety profile with mostly mild or moderate, reversible adverse events; no dose-limiting toxicities observed.

• All three patients demonstrated early signs of disease modification, including improvements or stabilization in biomarkers and clinical parameters.

• RP-A601 promoted increased PKP2 expression and desmosomal localization, with associated increases in desmocollin and cadherin, indicating functional remodeling of cardiac cell junctions.

• Two patients improved from NYHA Class II to Class I, with significant increases in KCCQ scores, reflecting better quality of life and heart function.

• Reductions in arrhythmia burden, including PVCs and NSVTs, were observed, though variability exists and comprehensive assessment is emphasized.

Dose selection and next development steps

• The 8E13 vg/kg dose was selected based on preclinical data, plateauing protein expression, and early efficacy signals; higher doses were deemed unnecessary and potentially less safe.

• No further dose escalation is planned; this dose will be used in the next phase, potentially a pivotal trial.

• Longer patient follow-up is expected to inform final endpoints and trial design, with regulatory discussions forthcoming.

• The pivotal study will initially target a similar patient population as phase I, with future plans to expand to younger and less advanced patients.

Safety, durability, and manufacturing

• Most adverse events were linked to immunosuppression, not the gene therapy; the safety regimen is considered appropriate for the selected dose.

• Long-term safety monitoring will continue, with no late-onset or ICD-specific gene therapy concerns anticipated based on current and prior AAV program experience.

• Durability is expected to be strong, drawing from up to five years of data in a related program, as cardiomyocytes do not turn over.

• Manufacturing capacity is secured for several years, with in-house facilities supporting both this and other programs.